| First Author | Sano R | Year | 2012 |
| Journal | Genes Dev | Volume | 26 |
| Issue | 10 | Pages | 1041-54 |
| PubMed ID | 22588718 | Mgi Jnum | J:184506 |
| Mgi Id | MGI:5424262 | Doi | 10.1101/gad.184325.111 |
| Citation | Sano R, et al. (2012) Endoplasmic reticulum protein BI-1 regulates Ca2+-mediated bioenergetics to promote autophagy. Genes Dev 26(10):1041-54 |
| abstractText | Autophagy is a lysosomal degradation pathway that converts macromolecules into substrates for energy production during nutrient-scarce conditions such as those encountered in tumor microenvironments. Constitutive mitochondrial uptake of endoplasmic reticulum (ER) Ca(2+) mediated by inositol triphosphate receptors (IP(3)Rs) maintains cellular bioenergetics, thus suppressing autophagy. We show that the ER membrane protein Bax inhibitor-1 (BI-1) promotes autophagy in an IP(3)R-dependent manner. By reducing steady-state levels of ER Ca(2+) via IP(3)Rs, BI-1 influences mitochondrial bioenergetics, reducing oxygen consumption, impacting cellular ATP levels, and stimulating autophagy. Furthermore, BI-1-deficient mice show reduced basal autophagy, and experimentally reducing BI-1 expression impairs tumor xenograft growth in vivo. BI-1's ability to promote autophagy could be dissociated from its known function as a modulator of IRE1 signaling in the context of ER stress. The results reveal BI-1 as a novel autophagy regulator that bridges Ca(2+) signaling between ER and mitochondria, reducing cellular oxygen consumption and contributing to cellular resilience in the face of metabolic stress. |
